5-Fluorouracil (hereinafter referred to as 5-FU) is widely used in treating various cancers, mainly gastrointestinal cancers, singly or in combination with other anticancer agents. However, 5-FU itself has only a weak antitumor effect and causes various side effects, such as diarrhea, stomatitis and others due to gastrointestinal toxicity, and myelosuppression. Therefore, it is difficult to say that 5-FU is always easy to use for cancer patients. To solve these problems, various orally administered 5-FU derivatives are under development; however, satisfactory clinical effects have not yet been obtained. The probable reasons for that are as follows. 5-FU is promptly decomposed in vivo by dihydropyrimidine dehydrogenase (hereinafter referred to as DPD), which is contained, in particular, in liver and tumor tissues; therefore, it is difficult to attain a sufficient antitumor effect corresponding to its dosage. 5-FU is uptaken not only into cancer cells but also into normal cells, such as marrow cells and gastrointestinal mucosa cells, and converted to active metabolites by the action of orotate phosphoribosyl trasnferase (hereinafter referred to as OPRT). Such active metabolites cause cell damage, i.e., they have cytotoxicity; therefore, their antitumor effect and side effects are not well balanced.
Compounds having a DPD inhibitory activity and an antitumor activity have been reported as examples of 5-FU derivatives (see patent literature 1 to 3). Among these, PLT 2 specifically discloses Compound (1) shown below, which is a compound generally known as Emitefur (also referred to as BOF-A2). A clinical trial was conducted to evaluate Emitefur; however, its development was discontinued, since it had strong side effects.

As described above, 5-FU derivatives that can enhance the antitumor effect by suppressing the decomposition of 5-FU in vivo and, at the same time, reduce the side effects have not yet been developed. Therefore, it is necessary to develop a novel 5-FU derivative having an enhanced antitumor-effect and low toxicity to improve the therapeutic effect for treating cancer patients.
As described above, there have been no reports about a derivative having an antitumor activity in addition to a DPD inhibitory activity and an OPRT inhibitory activity in one compound. Therefore, the development of a drug that achieves a balance between effects and toxicity, i.e., having a strong antitumor effect on human cancers and reduced gastrointestinal damage, and that improves the QOL of cancer patients is demanded.